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Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage.

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Title: Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage.
Authors: Shalvarjian, Katie E.1, Chadwick, Grayson L.2, Pérez, Paloma I.2, Woods, Philip H.3, Orphan, Victoria J.3,4, Nayak, Dipti D.1,2 dnayak@berkeley.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 11/11/2025, Vol. 122 Issue 45, p1-11. 151p.
Subjects: Methanogens, Stop codons, Pyrrolidine, Genetic code, Methane, Protein synthesis
Abstract: Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These nonstandard amino acids are beneficial as they facilitate novel biochemical reactions. However, code expansion leads to ambiguity at the recoded stop codon, which can either be read-through or terminated. Pyrrolysine (Pyl) is encoded by the amber codon (TAG/UAG) and is widespread in archaea, where it is required for methylamine-mediated methanogenesis, an environmentally important metabolism. Mechanisms to conditionally suppress the amber stop codon for Pyl installation during protein synthesis have not been identified. In the model methanogen, Methanosarcina acetivorans, we demonstrate that the UAG codon encodes dual meaning as stop and Pyl. Our data suggest that expression of Pyl biosynthesis and incorporation genes is tuned to the cellular demand for Pyl, which might allow these archaea to navigate ambiguous stop decoding in response to environmental cues. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 189542145
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  Data: Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage.
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  Data: <searchLink fieldCode="AR" term="%22Shalvarjian%2C+Katie+E%2E%22">Shalvarjian, Katie E.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chadwick%2C+Grayson+L%2E%22">Chadwick, Grayson L.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Pérez%2C+Paloma+I%2E%22">Pérez, Paloma I.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Woods%2C+Philip+H%2E%22">Woods, Philip H.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Orphan%2C+Victoria+J%2E%22">Orphan, Victoria J.</searchLink><relatesTo>3,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Nayak%2C+Dipti+D%2E%22">Nayak, Dipti D.</searchLink><relatesTo>1,2</relatesTo><i> dnayak@berkeley.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 11/11/2025, Vol. 122 Issue 45, p1-11. 151p.
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  Data: <searchLink fieldCode="DE" term="%22Methanogens%22">Methanogens</searchLink><br /><searchLink fieldCode="DE" term="%22Stop+codons%22">Stop codons</searchLink><br /><searchLink fieldCode="DE" term="%22Pyrrolidine%22">Pyrrolidine</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+code%22">Genetic code</searchLink><br /><searchLink fieldCode="DE" term="%22Methane%22">Methane</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+synthesis%22">Protein synthesis</searchLink>
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  Data: Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These nonstandard amino acids are beneficial as they facilitate novel biochemical reactions. However, code expansion leads to ambiguity at the recoded stop codon, which can either be read-through or terminated. Pyrrolysine (Pyl) is encoded by the amber codon (TAG/UAG) and is widespread in archaea, where it is required for methylamine-mediated methanogenesis, an environmentally important metabolism. Mechanisms to conditionally suppress the amber stop codon for Pyl installation during protein synthesis have not been identified. In the model methanogen, Methanosarcina acetivorans, we demonstrate that the UAG codon encodes dual meaning as stop and Pyl. Our data suggest that expression of Pyl biosynthesis and incorporation genes is tuned to the cellular demand for Pyl, which might allow these archaea to navigate ambiguous stop decoding in response to environmental cues. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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        Value: 10.1073/pnas.2517473122
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      – Code: eng
        Text: English
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        Type: general
      – SubjectFull: Stop codons
        Type: general
      – SubjectFull: Pyrrolidine
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      – SubjectFull: Genetic code
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      – SubjectFull: Methane
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      – SubjectFull: Protein synthesis
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      – TitleFull: Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage.
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              Text: 11/11/2025
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